Negative Affectivity, Depression, and Resting HRV as Possible Moderators of Endogenous Pain Modulation in.., 2018, Van den Bergh et al

Andy

Retired committee member
Negative Affectivity, Depression, and Resting Heart Rate Variability (HRV) as Possible Moderators of Endogenous Pain Modulation in Functional Somatic Syndromes

Background: Several studies have shown that patients with functional somatic syndromes (FSS) have, on average, deficient endogenous pain modulation (EPM), as well as elevated levels of negative affectivity (NA) and high comorbidity with depression and reduced resting heart rate variability (HRV) compared to healthy controls (HC). The goals of this study were (1) to replicate these findings and (2) to investigate the moderating role of NA, depression, and resting HRV in EPM efficiency within a patient group with fibromyalgia and/or chronic fatigue syndrome (CFS). Resting HRV was quantified as the root mean square of successive differences between inter-beat intervals (RMSSD) in rest, a vagally mediated time domain measure of HRV.

Methods: Seventy-eight patients with fibromyalgia and/or CFS and 33 HC completed a counter-irritation paradigm as a measure of EPM efficiency. Participants rated the painfulness of electrocutaneous stimuli (of individually calibrated intensity) on the ankle before (baseline phase), during (counter-irritation phase) and after (recovery phase) the application of a cold pain stimulus on the forearm. A larger reduction in pain in the counter-irritation phase compared to the baseline phase reflects a more efficient EPM.

Results: In contrast to our expectations, there was no difference between pain ratings in the baseline compared to counter-irritation phase for both patients and HC. Therefore, reliable conclusions on the moderating effect of NA, depression, and RMSSD could not be made. Surprisingly, patients reported more pain in the recovery compared to the counter-irritation and baseline phase, while HC did not. This latter effect was more pronounced in patients with comorbid depression, patients who rated the painfulness of the counter-irritation stimulus as high and patients who rated the painfulness of the electrocutaneous stimuli as low. We did not manage to successfully replicate the counter-irritation effect in HC or FSS patients. Therefore, no valid conclusions on the association between RMSSD, depression, NA and EPM efficiency can be drawn from this study. Possible reasons for the lack of the counter-irritation effect are discussed.
Open access at https://www.frontiersin.org/articles/10.3389/fpsyg.2018.00275/full
 
Several studies have shown that patients with functional somatic syndromes (FSS) have, on average, deficient [blah, blah, blah]

Seventy-eight patients with fibromyalgia and/or CFS and 33 HC completed a counter-irritation paradigm as a measure of EPM efficiency.

We did not manage to successfully replicate the counter-irritation effect in HC or FSS patients. Therefore, no valid conclusions on the association between RMSSD, depression, NA and EPM efficiency can be drawn from this study.

My paradigm for countering irritation is to walk away from this thread and go and have breakfast.
 
That would be evidence for PEM, and hence perhaps not so surprising.

Yes, I wasn't sure I understood that, as I've only read the abstract, but that thought occurred to me too - if ME patients had delayed pain following the painful stimulus, unlike healthy controls, that seems to imply some sort of biological delayed recovery process, maybe like PEM.

Although I dismissed this trial because of the psychosomatic assumptions they thought they were testing, it may actually have value in that it helps to disprove those psychosomatic assumptions, and comes up with an unexpected (to them) difference not explained by their BPS assumptions. Maybe it's another small nail in the BPS coffin.
 
It is very honest for a study in this domain... Usually, people in this area just keep looking till they find something in their data that does support their conclusions and report that. These guys actually admit that the results surprised them!

One of these days someone in the area will actually do a study, be surprised by the results, and actually change their view as a result.

We got to the surprise bit - well done! I wonder how many decades till they make the next big step.
 
It is very honest for a study in this domain... Usually, people in this area just keep looking till they find something in their data that does support their conclusions and report that. These guys actually admit that the results surprised them!

One of these days someone in the area will actually do a study, be surprised by the results, and actually change their view as a result.

We got to the surprise bit - well done! I wonder how many decades till they make the next big step.

Haha! Indeed. I have to admit I read that and went, hey, they actually said straight out they were surprised.

I can't quite figure out their possible reasons why their findings are different from expectations.

1. It wasn't painful enough
2. The participants were all women
3. The participants had already been through a 2h test prior to this one and might be tired/fatigued.
4. The participants were talked up for the test, were aware of what would happen and watched the procedure.


Firstly, OK, 1. could be a reasonable challenge to the results. 2. They state they chose women to keep the cohort to match the general numbers of patients anyway, so this is no challenge. 3. only reinforces that the results are unexpected. They even say that tiredness is a major contributor in pain sensitisation so the participants should feel it more, not less. 4. Just proves that those already anticipating pain, seeing it coming, getting the pain they expected, are NOT sensitised. Acc to their first hypothesis the subjects should feel it more since they see it coming and are already in pain from their own illness. They should be fearful and anxious thus making it hurt more. Their challenges only further prove their results!

"Since in our study pain ratings in the recovery phase were higher than pain ratings in both baseline and counter-irritation phase, but only in patients and not in HC, this effect is difficult to interpret."


Does anyone else have thoughts on this? I read it but it wasn't particularly clear as to what it was that the patients said hurt them more than the controls.
 
So for the baseline pain tolerance (electric shocks to the ankle and selection of an intensity for use later in the experiment) - there was no difference between patients and controls. Which suggests pain thresholds aren't different.

For the difference in the rating of the ankle electric shocks 1. before the application of a cold pack to the arm (Phase 1) and 2. after the application of the cold pack (Phase 2), there was no difference between patients and controls. This comparison was supposed to show that patients are less able to be distracted by another stimulus. But it didn't. In actual fact, neither patients nor controls showed the distraction effect. It's possible that this was because of a flaw in the design of the trial that had the subjects focusing on the pain after each shock to rate it, rather than rating at the end of each phase as has been done in other studies.

The one difference they did find was in Phase 3, after the removal of the cold pack. Patients found the ankle electric shocks a little bit more painful in this phase than they had in the other two phases while the controls didn't. But, it wasn't a big difference, so it's probably not worth getting very creative with an explanation unless it was replicated. Maybe the patients were just starting to get a bit fed up with the long series of experiments and questionnaires.

I'm surprised the researchers didn't make more of the fact that around half of the patients were taking some sort of analgesic. They did some comparisons of patients with and without analgesics- but it's not completely clear what they were comparing. They refer to comparisons of the ratings of the pain. So, it doesn't sound as if they compared the choice of the shock intensity at the beginning of the study between patients taking analgesics and those who did not, which would have been helpful in drawing conclusions about the patients' pain thresholds.

I find it an expression of the researchers' arrogance that people with fibromyalgia and people with CFS were all lumped together as the patient cohort. As in 'oh yes, all you people - it really doesn't matter that you have quite different symptoms because they are all equally imaginary'. At the very least, I would have thought the researchers would have been interested to do analyses of the group of people who rate pain as their most troublesome symptom and the group of people who rate PEM as their most troublesome symptom.

But it doesn't matter in the end, because this study really didn't tell us very much. Unfortunately, I doubt this is going to stop researchers continuing to give sick people electric shocks while suggesting that their pain control mechanisms are inferior.
 
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Thanks for all the summaries on this.

I find pain harder to manage as I get more run-down, so I'm a bit surprised that they didn't find a difference here. My expectation would have been that healthy people rate pain as worse when they're exhausted to when they're not. Maybe it's more that I find pain more upsetting as I get more run down in other ways, rather than the pain itself feeling worse?
 
Thanks, @Hutan, you made it sound much more clear. I am surprised that they found the returning sensation from cold to room temp was not more painful in everybody. It doesn't surprise me. And, yes, if certain ones were taking pain killing meds then, what the hell is the point to it? It won't yield any helpful results. Agree with your observation about lumping 'all you people' - what? who are 'sensitive types'? Who complain of 'unrealistic' pain, - yes, that's probably it. It's very clear what they think of Fibromyalgia, ME/CFS, and other 'functional' complaints - all the same root cause.

@Esther12 , I think that the more fatigued your body is, the more effort it takes to control and resist anything that takes energy, pain being a big one. Nothing like pain to bleed the resources dry. Maintaining regular responses to pain stimuli is one of them. Animals react with snaps and attacks if they are in pain, not just from being touched in the spot. They just don't have the tolerance for to be doing other things. They tend to get very thin just from coping with it. We do so many things when we're coping with pain from trying to sit up, talk, eat, digest, move - all manner of things so resistance gets lowered by each degree some other effort has to be made.

Pain receptors, surely, can only be reduced by removing pain that causes them, just as receptors are reduced in every other way, not in tricking the body or training it to be more resistant. If they aren't there, then the person isn't going to react, no matter what illness they have, surely. I mean, apart from memories of traumatic pain, sure the person may be leary of triggers for a while but in the face of evidence of no pain then they'll eventually relax physically. I don't get this theory of psychogenic pain at all. How does the body 'learn' to be in pain and maintain it when there is no stimulus? Surely there would be no receptors.
 
I am surprised that they found the returning sensation from cold to room temp was not more painful in everybody.
In the third phase, after the cold pack was taken away, patients rated the electric shocks to the ankle as, on average, a bit more painful, even though the electric shocks were the same intensity throughout. So, they weren't actually rating the pain of the cold pack. The researchers were expecting that during the Phase 2, healthy people would be distracted by the cold pack and rate the ankle pain lower than in Phase 1 and Phase 3 (which didn't happen).

I think that the more fatigued your body is, the more effort it takes to control and resist anything that takes energy, pain being a big one.
You are so right, that is my experience. So conceivably the reason the ratings of the ankle pain went up in Phase 3 for patients was that, on average, after nearly 2 hours of the study including dealing with pain, they were exhausted.
 
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